Research in Molecular Medicine

en Uric Acid-to-Albumin Ratio and Its Association with Oxidative Stress Markers in Type 2 Diabetes Mellitus with and without Diabetic Nephropathy بیوشیمی Biochemistry پژوهشي Research <div style="text-align: justify;">Background: This study evaluated the uric acid-to-albumin ratio (UAR) and its association with oxidative stress markers and clinical parameters in patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy (DN). Methods: In this comparative cross-sectional study, diabetic patients were divided into two groups: T2DM with nephropathy and T2DM without complications. Clinical, biochemical, oxidative stress, and inflammatory markers were assessed. UAR was calculated and compared between groups. Correlations between UAR and metabolic, oxidative, inflammatory, and lipid parameters were analyzed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of UAR for DN. Results: Patients with DN had significantly lower serum albumin levels and higher UAR values compared with uncomplicated diabetic patients (1.15 ± 0.33 vs. 1.09 ± 0.26, p = 0.047). Serum creatinine was significantly higher, whereas HDL and LDL cholesterol levels were lower in the DN group. UAR demonstrated a significant inverse correlation with reduced glutathione (GSH) (r = −0.364, p = 0.013) and HDL cholesterol (r = −0.250, p = 0.034), as well as positive correlations with the neutrophil-to-lymphocyte ratio (NLR) (r = 0.254, p = 0.031). No significant associations were observed between UAR and total antioxidant capacity (TAC) or most lipid and glycemic parameters. ROC analysis demonstrated poor discriminatory ability of UAR for DN (AUC = 0.551, p = 0.426). Conclusion: UAR is modestly elevated in DN group and is associated with selected oxidative stress and inflammatory markers; however, its limited diagnostic performance restricts its utility as a standalone biomarker.</div> Type 2 diabetes mellitus, Diabetic nephropathy, Uric acid-to-albumin ratio (UAR), Oxidative stress, Glutathione, Neutrophil-to-lymphocyte ratio, Albuminuria, Biomarkers, Renal dysfunction. 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1355-1&slc_lang=en&sid=1 Liela Jihad Kahayit Al-shebillawy laylajihad59@gmail.com No Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Masoumeh Rezaei Talarposhti masoumehrezaei.cmb@gmail.com No Molecular and Cell biology Research Center,Faculty of Medicine , Mazandaran University of Medical Sciences , Sari , Iran Zahra Alikhani zahraalikhani789@gmail.com No Department of Medical Microbiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran Hossein Mokhtari mokhtarimsh@yahoo.com No Amol faculty of paramedicine, Mazandaran university of medical sciences, Sari, Iran. Hadis Musavi msc.musavi66@gmail.com Yes Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Abbas Khonakdar-Tarsi khonakdarab@gmail.com No Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

en Immunoinformatics-Guided Design and Structural Validation of a Multi-Epitope Vaccine Candidate Targeting Gastric Cancer–Associated Membrane Proteins زیست شناسی مولکولی Molecular biology پژوهشي Research <div style="text-align: justify;">Background: Epitope-based cancer vaccines require rigorous safety filtering and structural validation to overcome translational limitations in heterogeneous malignancies such as gastric cancer. To design and computationally validate a safety-oriented multi-epitope vaccine targeting gastric cancer–associated membrane proteins. Methods: Extracellular domains of nine gastric cancer–associated membrane proteins were screened to identify CTL (9-mer) and HTL (15-mer) epitopes. Peptides with exact sequence matches to the human reference proteome were excluded as a preliminary self-similarity filtering step. Epitope prioritization was performed using NetMHCpan and NetMHCIIpan based on binding affinity and percentile rank. Selected candidates were evaluated for antigenicity, allergenicity, toxicity, proteasomal cleavage, and TAP transport efficiency. High-ranking epitopes were assembled using optimized linkers with an N-terminal β-defensin-3 adjuvant. Physicochemical properties, intrinsic disorder, and secondary structure were analyzed. The tertiary structure was predicted, refined, and validated using Ramachandran plot and TM-score metrics. Vaccine–HLA interactions were assessed by molecular docking and molecular dynamics simulations. Immune responses were simulated in silico, and codon optimization with in silico cloning was performed to evaluate expression feasibility. Results: Screening of extracellular domains from nine gastric cancer–associated membrane proteins generated 161–900 unique CTL and 109–894 HTL non-self peptides per antigen. Six epitopes were prioritized based on low percentile ranks (CTL ≤2; HTL ≤3.1) and favorable antigenicity (VaxiJen 0.51–0.99). The final 143–amino-acid construct showed a molecular weight of 15.54 kDa, instability index of 27.02, and GRAVY score of −0.435, indicating predicted stability and hydrophilicity. Structural refinement yielded 97.2% residues in favored/allowed Ramachandran regions (90.4% core) with RMSD 0.48 Å and TM-score 0.9886, confirming preservation of global topology. ClusPro docking identified the top-ranked clusters for both complexes, with weighted scores of −881.7 (HLA-A*02:01) and −878.3 (HLA-DR1). Molecular dynamics simulations showed rapid equilibration (~10 ns), stable RMSD, consistent radius of gyration, gradual SASA reduction, and persistent hydrogen bonds. Codon optimization achieved a CAI of 1.0 and GC content of 50.82%, supporting expression feasibility. Conclusion: This integrative strategy provides a computationally prioritized and structurally validated multi-epitope vaccine candidate. Nevertheless, the applied filtering strategy represents only a preliminary risk-reduction approach, and all findings require experimental validation.</div> Cancer vaccine design, Gastric cancer, Immunoinformatics, Multi-epitope vaccine, Structural vaccinology, T-cell epitopes 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1467-1&slc_lang=en&sid=1 Kianoush Mohammadi kianoush.mohammadi@tabrizu.ac.ir No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Reza Safaralizadeh safaralizadeh@tabrizu.ac.ir Yes Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Elham Safarzadeh elham.im63@gmail.com No Cancer Immunology and Immunotherapy Research Center,Ardabil University of Medical Sciences, Ardabil, Iran Ali Shamsazar ali.shamsazar@uma.ac.ir No Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

en Clinical Level of the Long Non-Coding RNA Taurine Upregulated Gene 1 as a Predictive Biomarker in Neoplasms: A Systematic Review بیوشیمی Biochemistry review review Background: Long non-coding RNAs (lncRNAs) are important regulators of cancer development and progression. Taurine upregulated gene 1 (TUG1) has been proposed as a prognostic biomarker in several malignancies, although its clinical significance remains inconsistent. This systematic review evaluated the available evidence on the association between TUG1 expression and prognosis in patients with cancer. Methods: A systematic literature search was conducted on the Web of Science, PubMed, Scopus, ProQuest, ERIC, and ScienceDirect for studies published between January 2014 and December 2023. Original studies investigating the relationship between TUG1 expression and cancer prognosis were included. Data on study characteristics, cancer type, sample size, TUG1 detection method, follow-up, survival outcomes, and principal findings were extracted independently by two reviewers and synthesized qualitatively. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Results: Twenty studies were included. Most reported that elevated TUG1 expression was associated with poor prognosis, including shorter overall survival, reduced disease-free survival, tumor progression, recurrence, metastasis, and chemoresistance. These findings were consistently observed in hepatocellular carcinoma, colorectal cancer, bladder cancer, renal cell carcinoma, esophageal squamous cell carcinoma, osteosarcoma, acute myeloid leukemia, and Philadelphia chromosome-negative acute lymphoblastic leukemia. In contrast, inconsistent results were reported for lung cancer and glioma, where higher TUG1 expression was associated with improved survival or showed no significant prognostic value in some studies. Study quality ranged from moderate to high (NOS scores: 6–8). Conclusion: Current evidence suggests that TUG1 is a promising prognostic biomarker in several malignancies. However, its prognostic significance appears to be cancer-specific, highlighting the need for large prospective studies to confirm its clinical utility.   long non-coding RNA, TUG1, cancer, prognosis, survival, biomarker, systematic review 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1421-1&slc_lang=en&sid=1 Parisa Bahavar bahavarparisa72@gmail.com No Fatemeh Sadat Hosseini malakekavir4479@gmail.com No Mohammad Amin Rezaei msc.musavi66@gmail.com No Mehrdad Payandeh Shaghayegh.msc75@gmail.com No Amirreza Rahimi vidzishirazi@gmail.com No Hooman Zarei hooman1634zarei@gmail.com Yes

en Ameliorative effect of Calendula persica against ZnO nanoparticles cytotoxicity on human hepatoma HepG2 cells بيولوژي Biology پژوهشي Research <div style="text-align: justify;">Background: The extensive application of zinc oxide nanoparticles (ZnO NPs) in a wide range of consumer and industrial products has resulted in increased human exposure to these nanomaterials. Calendula persica (C. persica) is a traditional medicinal plant that has been used in folk medicine for the treatment of various diseases. Materials and Methods: In the present study, we investigated the potential ameliorative effect of C. persica extract against ZnO NP-induced cytotoxicity in HepG2 cells. The cytotoxic effects of different concentrations of ZnO nanoparticles, as well as the protective role of C. persica extract, were evaluated in HepG2 cells. Morphological alterations were first assessed using microscopic examination. Subsequently, cell viability was determined using neutral red uptake and MTT assays. Results: Exposure to higher concentrations of ZnO NPs resulted in pronounced morphological alterations and significantly increased cell mortality in HepG2 cells. In contrast, treatment with C. persica markedly attenuated ZnO NP-induced morphological damage and reduced cell mortality, suggesting a protective effect against nanoparticle-mediated cytotoxicity. Conclusion: In conclusion, C. persica extract exhibited significant protective effects against ZnO NP-induced cytotoxicity in HepG2 cells, as evidenced by its ability to attenuate cellular damage and improve cell viability. These findings suggest that C. persica may serve as a promising natural agent for mitigating nanoparticle-induced cellular toxicityBackground: The extensive application of zinc oxide nanoparticles (ZnO NPs) in a wide range of consumer and industrial products has resulted in increased human exposure to these nanomaterials. Calendula persica (C. persica) is a traditional medicinal plant that has been used in folk medicine for the treatment of various diseases. Methods: In the present study, we investigated the potential ameliorative effect of C. persica extract against ZnO NP-induced cytotoxicity in HepG2 cells. The cytotoxic effects of different concentrations of ZnO nanoparticles, as well as the protective role of C. persica extract, were evaluated in HepG2 cells. Morphological alterations were first assessed using microscopic examination. Subsequently, cell viability was determined using neutral red uptake and MTT assays. Results: Exposure to higher concentrations of ZnO NPs resulted in pronounced morphological alterations and significantly increased cell mortality in HepG2 cells. In contrast, treatment with C. persica markedly attenuated ZnO NP-induced morphological damage and reduced cell mortality, suggesting a protective effect against nanoparticle-mediated cytotoxicity. Conclusion: In conclusion, C. persica extract exhibited significant protective effects against ZnO NP-induced cytotoxicity in HepG2 cells, as evidenced by its ability to attenuate cellular damage and improve cell viability. These findings suggest that C. persica may serve as a promising natural agent for mitigating nanoparticle-induced cellular toxicity</div> Zinc oxide nanoparticles, HepG2 cells, cytotoxicity, C. persica 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1266-2&slc_lang=en&sid=1 Ehsan Zayerzadeh zayerzadeh@standard.ac.ir Yes Food Toxicology Research Group, Research Center of Food Technology and Agricultural Products, Standard Research Institute, Karaj, Iran Mohammad Kazem Koohi Mkkoohi@ut.ac.ir No Division of Toxicology, Department of Comparative Bioscience, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

en Laurencia caspica extract strongly induces CYP2D6 transcription besides stabilizes its intra-tissue Diazinon-induced transcriptional fluctuations within AGS cells زیست شناسی مولکولی Molecular biology پژوهشي Research Introduction Cytochrome P450 (CYP) isoform 2D6, the second most abundant CYP enzymes in the body involving in the oxidative metabolism of a large number of endogenous and exogenous compounds, is of key relevance for transcription alteration-modulated carcinogenesis. However, absence of a known biological inducer besides of its frequent transcriptional changes made its application challenging. Transactivatory potential of Laurencia caspica extract for CYP2D6 transcription was evaluated in AGS cells in an attempt to rectify its Diazinon-induced fluctuations. Materials and Methods Cytotoxicity of Diazinon and L. caspica ethanol extract as well, was studied on AGS cells using MTT assay. mRNA levels of CYP2D6 were quantitatively estimated using real-time PCR analysis following treatment of the cells with 0-10 μM concentrations of Diazinon or 0-40 μg/ml of L. caspica extract as well as following their co-treatment. The later one, including treatment with 0.1 μM concentration of Diazinon of the cells pre-treated with various concentration ranges of L. capsica extract, was scheduled to evaluate the protective efficacy of L. caspica extract against CYP2D6 transcriptional changes induced following Diazinon treatment. All tests were carried out three times each in triplicate and the results expressed as mean ± standard deviation. Results MTT assay revealed IC50 values of 80 µM and 840 µg/ml for Diazinon and L. capsica extract, respectively. Interestingly, L. capsica extract showed proliferative activity at the concentrations up to 70 µg/ml. qRT-PCR results of the independent experiments from Diazinon treatment revealed irregular transcription fluctuations of CYP2D6. Yet, mean of all data produced a bell-shaped curve in which the 0 and 10 μM treatment caused highest CYP2D6 down-regulation while its transcription remained unchanged with 1 μM Diazinon. When treating with L. caspica extract, CYP2D6 transcription was strongly and steadily incited thereby a 4-fold increase of the mRNA level was induced at highest extract (40 µg/ml) concentration. Similarly, treatment of the cells with 0.1 µM Diazinon of the cells pre-treated with various concentrations of L. caspica extract revealed a dose-dependent transcription up-regulation similar to that of the L. caspica itself, particularly at higher concentrations. Conclusions Ethanol extract from L. caspica has antioxidant and proliferative activities at lower concentrations. It is a strong inducer for CYP2D6 transcription and could rectify Diazinon-induced CYP2D6 fluctuations. Bioactive molecules from L. caspica are promising candidate for detoxification of the chemotherapy drugs particularly in gastric cancer patients.   AGS cell line, CYP2D6, Diazinon, Gastric cancer, Laurencia capsica, Transcription induction 0 0 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-779-3&slc_lang=en&sid=1 Shima Yahoo-Torghabe shimayahoo.t@gmail.com No Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran. Zahra Hosseini-Khah zahra_582005@yahoo.com No Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran Ali Barzegar alibar647@yahoo.com Yes Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran Ali Pakdin-Parizi ali.pakdin@gmail.com No Genetics and Agricultural Biotechnology Institute of Tabarestan, Sari Agricultural Sciences and Hossein Dehdari hoseyn_dehdari@yahoo.com No Department of Basic Sciences, Sari Agricultural Sciences and Natural Resources University, Sari, Iran Leili Sadeghiamiri leilasadeghi_1370@yahoo.com No Tissue Engineering Department, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.